There is increasing evidence that behavioral and hormonal factors alter progression of aging and Alzheimer's Disease (AD). Such knowledge has great implications for strategies to prevent cognitive decline. The rodent model will be used to evaluate two factors that human research suggests alter age- and disease- related changes: prior cognitive experience and a high fat diet. 1) Prior cognitive experience: Does using it prevent you from losing it? People who stay mentally active show less age-related cognitive decline. Animal work addressing this has only used males, and the limitations of cognitive practice have not been detailed. One male and one female group will receive no maze testing, while another will receive only procedural components of testing. The other male and female rats will receive either working or reference memory cognitive practice throughout life, and then spatial and non-spatial working and reference memory testing when they become aged to evaluate whether memory transfer effects occur. Also, we recently found that both-cognitive testing and aging altered neurotrophins. We hypothesize that these alterations due to cognitive testing protect against age-related memory decline. Specific Aim 1 tests the hypothesis that the mnemonic demands of cognitive practice affect whether cognitive practice procedures attenuate age-related neurotrophin and cognitive changes. 2) High fat/cholesterol (HF/HQ diet: Data suggest that a HF/HC diet is a risk factor for cognitive decline in aging and AD. We found that a HF/HC diet impaired memory in middle-aged male rats, and that testosterone treatment improved memory in aged male rats. Since human work found that testosterone treatment improved cognition and lipid profiles in older men, we question whether testosterone reverses the detrimental effects of a HF/HC diet. All animal studies testing effects of a high fat diet used young or middle-aged males. Since data suggest that males are more sensitive to adverse dietary conditions, we will evaluate the effects of a HF/HC diet in middle-aged males vs. females. In women, data suggest that menopause status affects cardiovascular risk factors such as lipid profiles. Middle-aged female rats can be grouped into state of "menopause" (estropause), which affords us the opportunity to evaluate interactions between reproductive senescence, HF/HC diet, and cognition. We will ovariectomize one group of middle-aged females, and divide intact females into estropause state to determine if ovarian hormone removal or reproductive senescence influences cognitive outcome of a HF/HC diet. Specific Aim 2 tests the hypotheses that middle-aged females, like males, show cognitive impairment due to a HF/HC diet depending on state of estropause, and that testosterone attenuates the detrimental effects of a HF/HC diet in middle-aged males. After the maze battery, rats from both studies will have neurotrophin levels assayed in cognitive brain regions.